Malignant tumours belong to the top 10 leading causes of death in the upper-middle and high income countries. Malign tumour cells are characterized by their unchecked growth, spreading throughout the body (migration and metastasis) and their invasion of healthy tissues. Malignant tumors overcome multiple barriers, including the extracellular matrix, before invading blood or lymph vessels on their way to spread throughout the body. In particular their ability of tissue invasion followed by establishment and growth of metastases is responsible for the lethality of cancer, because vital organs such as the lung are affected.
Commonly used compounds for the treatment of cancer such as cytostatics have an effect on all rapidly dividing cells in the body, whether they are cancerous or not. Particularly problematic is the effect on hematopoietic stem cells in the bone marrow, which leads to a rapid decline in white blood cell count and in consequence immunosuppression. This severely limits the use of cytostatics in many patients. A strategy that only targets a certain subset of cells, including cancer cells, could overcome these limitations.
According to recent research cancer cells can be thought of as cells partially retransformed into embryonic stem cells. Similar to embryonic stem cells in the uterus, they try to migrate and invade tissues able to support them (Mani et al., Cell 133, 704-715; 2008; Polyak and Weinberg, Nature Reviews Cancer 9, 265-273; 2009).
Without expression of stem cell specific genes, cancer cells lose their ability to migrate and invade other tissues. Therefore, selective ablation of stem cell specific genes in cancer cells could be a novel therapeutic opportunity. One example of a stem cell specific gene that has been linked to cancer is Oct4.
Particularly synthetic siRNA or natural microRNAs would be suitable as therapeutics. MicroRNAs are naturally occurring regulators of gene expression that represent an evolutionarily conserved gene regulatory mechanism existing in invertebrates and vertebrates. A variety of microRNAs are involved in the support of stem cells or in the initiation of stem cell differentiation into tissue specific cell types (Lichner et al., 2011, Differentiation 81, 11-24; Lüningschrör et al., 2012, Stem Cells 30, 655-664). Interestingly, some of these microRNAs are also associated with cancer.
The problem underlying the present invention is to provide microRNAs suitable for the treatment of malign tumour cells. This problem is solved by the subject-matter of the independent claims.